Severity of perinatal asphyxia brain injury induces opposite effects in cocaine sensitization

EDUARDO BLANCO-CALVO1, PABLO GALEANO2, JUAN I. ROMERO2, MARÍA J. LUQUE-ROJAS3, LUIS J. SANTÍN-NÚÑEZ1, FERNANDO RODRÍGUEZ DE FONSECA3, FRANCISCO CAPANI

Congreso; FENS; 2012

FENS

Perinatal asphyxia has been considered as one of the most important causes of mental disorders in adulthood. Long-lasting neural deficits associated with asphyxia are related to a dysfunction of the brain's dopaminergic system. Likewise, some of the behavioural outcomes of these alterations may be related with sensitization to psychostimulants and addiction processes.   Therefore, the aim of the present study was to examine the effects of perinatal asphyxia in locomotor sensitization to cocaine following a repeated administration protocol. Moreover, we analysed whether cocaine induced changes in the expression of functional markers of dopamine in the dorsal striatum. Rats were born vaginally (CTL), by caesarean section (C+), or by caesarean section following moderate (15 min, PA15) or severe (19 min, PA19) asphyxia. At three months of age, animals were evaluated in a cocaine induced behavioural sensitization protocol, and tyrosine hydroxylase levels were measured by immunohistochemistry and Western-blot.   All groups showed a normal conditioned locomotion after cocaine conditioning, but PA19 and PA15 exhibited an ameliorated and increased behavioural sensitization response induced by cocaine priming, respectively. These behavioural alterations were associated to changes on the expression of tyrosine hydroxylase in the dorsal striatum of PA15 and PA19 animals showing an increasing and decreasing in the levels of this enzyme, respectively. These findings suggest that the severity of perinatal asphyxia (moderate at PA15 or severe at PA19) might induce different responses in cocaine sensitization depending on the overactivation or damage through the dopaminergic activity in the dorsal striatum. In conclusion, the severity of acute perinatal hypoxia brain damage might determinate the behavioural alterations associated with the psychostimulants sensitization through the modulation of the brain dopaminergic system.